Driven by the hypothesis that many of the most severe neuropsychiatric disorders of childhood onset are manifestations of deviations from the path of normal brain development, the anatomical substrates of which can be detected by magnetic resonance imaging (MRI), our team has been acquiring and analyzing brain MRI scans from healthy and psychiatrically ill children, adolescents, and adults. The study design is longitudinal to assess not only brain size or shape differences but to map out the developmental curves for a variety of brain structures in health and in illness. Combining the brain imaging information with extensive behavioral and neuropsychological testing as well as genetic data allows us to explore the relationship between genes, brain, and behavior. Clinically, the project encompasses the largest imaging studies of ADHD and Childhood-Onset Schizophrenia. Seminal contributions to the literature have been produced in each of these areas. The normative development component utilizes the world's largest collection of well-characterized pediatric brain MRI scans (N = 1000) and serves as a resource for many neuroimaging projects throughout the world. To assess sex differences in the brain, we are examining subjects with variations in the number of X and Y chromosomes (i.e. Klinefelter Syndrome, XXXY) and subjects with hormone anomalies (i.e. Cushings disease, Congenital Adrenal Hyperplasia, Familial Precocious Puberty). To assess nature/nurture questions we are studying brain development in mono and dizygotic twins.